Retrospective study of association of DNA damage response and repair gene mutations and clinical outcomes of biliary tract cancer

A retrospective study at Sichuan University (Chengdu, China) investigated the association of deleterious DNA damage response and repair (DDR) gene mutation with clinical outcomes of patients receiving first-line chemotherapy with or without immunotherapy for biliary tract cancer (BTC). Among patients receiving chemotherapy, DDR mutation-positive compared with negative patients had higher overall response rate (50.0% versus 14.9%; p=0.001), longer median progression-free survival (7.7 versus 3.8 months; p=0.001), and longer median overall survival (28.6 versus 11.9 months; p<0.001). In multivariate analysis DDR gene mutations were independently associated with prolonged mPFS (HR 0.37; pxtagstartz0.001) and mOS (HR 0.19; p<0.001). Among patients receiving chemotherapy plus immunotherapy, DDR mutation-positive compared with negative patients had higher overall response rate (45.8% versus 8.3%; p=0.001), longer mPFS (7.7 versus 3.8 months; p=0.009), and longer mOS (12.7 versus 8.8 months; p=0.011). In multivariate analysis, presence of DDR gene mutations was associated with longer mPFS (HR 0.34; p=0.005) and mOS (HR 0.23; p=0.004). The authors conclude that among patients receiving chemotherapy with or without immunotherapy for BTC, deleterious DDR gene mutations were associated with improved clinical outcomes.